Medication Assisted Therapy - Auburn Universitypharmacy.auburn.edu/oti/pdf/oti-jackson2.pdf · Learning Objectives •Define medication assisted therapy (MAT) •Discuss medications

Medication Assisted Therapy

Cherry W. Jackson, PharmD, BCPP, FASHP, FCCP

Professor of Pharmacy, Auburn University

Clinical Professor of Pharmacy, University of Alabama, Birmingham

1

Disclosure/Conflict of Interest

• I, Cherry Jackson, have no actual or potential conflict of interest in relation to this program.

2

Learning Objectives

• Define medication assisted therapy (MAT)

• Discuss medications to treat Opioid Use Disorder (OUD)

• Describe behavioral therapies to treat Opioid Use Disorder

• Discuss the role of mental health disorder treatment in the treatment of Opioid Use Disorder

• Demonstrate best practices in use of medication assisted therapy

3


www.ruralhealthinfo.org

https://www.samhsa.gov/medication-assisted-treatment/treatment 4

http://www.ruralhealthinfo.org/


5

What are the Benefits of Medication Assisted Therapy

www.drugs.com 6


SAMHSA. 2019

Foamcast.org7


• Decrease illicit opiate use and other criminal activity among people with substance use disorders

SAMHSA. 2019

Tonicvice.com 8


• Increase patients’ ability to gain and maintain employment

SAMHSA.2019

Columbusrecoverycenter.com9


• Improve birth outcome among women who have substance use disorders and are pregnant

SAMHSA.2019

Clinicalpainadvisor.com 10

Only Half of Addiction Treatment Centers Offer Medication Assisted Therapy

Private Facilities with MAT

Rehab with MAT Rehab without MAT

MAT Availability

Rehab with MAT Rehab without MAT

SAMHSA.2019 11

Court rules in favor of woman seeking opioid meds in jailBy Associated Press May 2,2019 | 4:52pm

New York Post. May,2 2019 12

Heroin and Opiate Relapse Are Approximately 80%

13


14

Myth: Medication Treatment Substitutes “One Addiction for Another”

FACT

• When properly prescribed medications used to treat addiction: Reduce drug cravings

Prevent relapse

Do not cause a “high”

SAMHSA.2019

Adler MW. NIDA Principles of Drug Addiction Treatment. 2012

Medicalequipmentservices.com 15

Myth: Addiction Medication are a “Crutch” that Prevents “True Recovery”

FACT

• Individuals stabilized on medication assisted therapy can achieve “true recovery” No illicit drugs

No euphoria

No sedation

No functional impairment

Do not meet criteria for addiction

White WL. The American Society of Addiction Medicine,

The ASAM Criteria. 2010

NIDA Drug Facts. 2009

Beachcrossers.com

16

Myth: Medication Assisted Therapy Should Not be Long Term

FACT

• There is not one-size-fit-all duration for medication assisted therapy Stabilization

Maintenance

Counseling

On-going rehabilitation

Treatment may be indefinite!

SAMHSA. 2019

NIDA. 2016

Killerinnovations.com17

MYTH: Requiring People to Taper Off Medication Assisted Therapy Helps Them Get Healthier Faster

FACT

• Requiring individuals to stop their addiction medications increases risk of relapse Tolerance fades rapidly

Opioid misuse may result in overdose

Day E. J Substance Abuse Treatment 2010;

1:56-66.

Therecoveryvillage.com18

MYTH: Courts are in a Better Position than Doctors to Decide Appropriate Drug Treatment

FACT

• Deciding the appropriate treatment should be between the patient and their physician Courts are not trained to make

medical decisions

White WL, The American Society of Addiction

Medicine: The ASAM Criteria. 2013.

Dreamstime.com19

Medications used to Treat Opioid Use Disorders

20

Medications Used to Treat Opiate Use Disorder

Methadone Controlled substance Must go to a clinic to

receive a dose These clinics must also

provide counseling Methadone acts at the

same place in the brain that opioids work

Brand names are Dolophine, Methadone and Methadone Intensol

Methadone reduces cravings and prevents withdrawal symptoms Treatment of patients with substance use disorders, second

edition. Am J Psychiatry. 2006; 163(8 suppl):5-82.

Opiateaddictionsupport.com21

Medications used to Treat Opiate Use Disorder

Methadone Treatment of choice if

pregnant

Dosing is individualized

Maintenance dose is usually 80-120 mg/day

Methadone must be stopped slowly and carefully.

Care has to be given around slowed breathing-avoid alcohol.

Other side effects are nausea, vomiting, headache, sleepiness, and constipation Treatment of patients with substance use disorders, second

edition. Am J Psychiatry. 2006; 163(8suppl):5-82.

Opiateaddictionsupport.com 22

Medications used to Treat Opioid Use Disorder

• Respiratory depression

• QTc interval prolongation

• Torsades de pointes

• Neonatal abstinence syndrome

• Drug-drug Interactions

CYP3A4

CYP1A2

CYP2D6

others

Kapur BM et al. Crit Rev Clin Lab Sci 2011;48(4):171-95.

Logan BA, et al. Clinical obstetrics and gynecology 2013;56(1):186-92.

Medicalnewstoday.com23

Medications Used to Treat Opiate Use Disorders

Buprenorphine

• Controlled substance given by trained physicians.

• Buprenorphine comes as a sublingual tablet, a film, and a long acting implant.

• Dose is 8-16 mg daily

• Avoid in liver disease

• Avoid with benzodiazepines.

• Side effects: sleepiness, stomach upset, constipation, headache, difficulty breathing

Buprenorphine (package insert). Roxane Pharma,

Columbus Ohio,2015.

Vox.com

24


Buprenorphine long acting

• Called Probuphine

• Consists of 4 one inch rods implanted under the skin

• Lasts for 6 months

• Clinical study shows it is equal to buprenorphine sublingual

Probuphine(package insert). Braeburn

Pharmaceutics Inc. Princeton, NJ

Cadth.ca

Buprenorphine long acting

25

Medications used to Treat Opiate Use Disorders

Sublocade Once a month injection

Forms a solid deposit or a “depot” which is released as the depot breaks down.

Patient has to be on transmucosal buprenorphine 7 days before starting Sublocade

Sublocade has more weeks without positive urine tests or report of opioid use versus placebo Sublocade (package insert) North Chesterfield

Virginia: Indivior PLE; 2018.

Matclinics.com 26


Buprenorphine-Naloxone

Preferred for maintenance

Ratio of bup:naloxone is 4:1

Names for sublingual films

Suboxone

Cassipa

Names for buccal films

Bunavail

Name for sublingual tablet

Zubsolv

Name of buccal film for pain

Belbuca

Name of patch for pain

ButransSuboxone (package insert). North Chesterfield,

Virginia: Indivior PLE; 2018

Clearbrookinc.com27


Naltrexone

Completely blocks the opiate receptor

Naltrexone blocks the effects of opioids, including pain meds.

No high

50 mg lasts 24-36 hours

Poor adherence limits its use

Minozzi S et al. Cochrane Database Syst Rev. Chichester, UK 2011; (2):

CD0013333. DOI: 10.1002/14651858.CD001333.pub3. PubMed PMID:

21318150.

Centerforlifesolutions.com 28


Naltrexone Injection Vivitrol is a long acting injection of

naltrexone.

Must complete a 7-10 day opioid withdrawal before starting Vivitrol

Good if highly motivated

Side effects include stomach cramps, headache dizziness, pain, tenderness, anxiety, nervousness, trouble sleeping, nausea, vomiting, tiredness.

Using opioids with Vivitrol can be fatal

Vivitrol (package insert). Waltham, MA: Alkermes, Inc

2015.

Verywellmind.com29

Medication Assisted Treatment

30

Behavioral Therapies to Treat Opioid Use Disorder

Cognitive Behavioral Therapy

Therapist uses thoughts, feelings to help change behaviors

Change usually takes 12-16 weeks

Improves self-control and self-confidence

It helps individuals to overcome and control and combat cravings

Actifyneuro.com 31


Dialectical Behavioral Therapy

Learn mindfulness

Learn distress tolerance

Learn emotional regulation

Leading to interpersonal effectiveness

Takes approximately 8 weeks

Includes ongoing work between sessions

Discoveryacademy.com 32

Behavioral Therapies to Treat opioid Use disorder

Mindfulness meditation

Cultivates better self-

awareness

Decreases stress

Improves coping skills

Prevents craving

Prevents relapseMindful.org 33

Behavioral therapies to treat opioid Use disorder

Motivational Interviewing

Often used as part of other therapies

Involves reflective and empathetic

listening

Allows discussion of areas of life that

needed change

Helps individuals develop self

efficacy

Outinperth.com 34


Narcotics Anonymous

12 step model

Developed for individuals

with substance use issues

Second largest 12-step

organization

Recovery-world.com 35

Treating Mental Health and Opioid Use Disorder

• Opiate addiction is a mental illness

• Opioids cause changes in brain chemistry

• Opiates can help people mentally escape situations that they are in

• Mental health issues and substance use issues must be treated together

• One left untreated will cancel any success with the other

Njprevent.com 36


• 16% of mentally ill use >50% of opioids

• 5% of those without mental illness use opioids

• Opioids may relieve both mental and physical pain-at least initially.

David M. J Am Board Fam Med 2017;30:407-17.

WindwardwayRecovery43


Depression Opiate Addiction Chronic Pain

Sleep disturbances

Hopelessness

Helplessness

Difficulty

concentrating

Low self-esteem

Pain

Increases fatigue

Numbing

Increased pleasure

Helps people sleep

Difficulty

concentrating

Feels like “super self”

Numbs pain

Increases fatigue

Stops release of

endogenous opiates

Sleep disturbances

Hopelessness

Helplessness

Difficulty

concentrating

Low self-esteem

Pain

Increases fatigue

Hooten WM. Mayo Clin Proc 2016; 91(7): 955-70.

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• Integrate the treatment as much as possible.

• The psychiatric disorder and SUDs are treated by the same clinician or in a single program

• The evidence-based treatment model is called integrated dual diagnosis treatment

• MAT for substance use is encouraged when options are available and appropriate. Manseau MW. From Patient Care to Public Health, 2018.

Americanaddictioncenters.org52

Treating Mental Health and Opioid Use Disorders

• MAT with XR naltrexone is the standard of care because it is associated with lower rates of negative outcomes

• Clinicians treating CODs including OUD must be able to deliver MAT.

• MAT with methadone, can only be dispensed in an opioid treatment programs (OTPs)

• It may be difficult for clinicians and programs prescribing buprenorphine and XR naltrexone to deliver a robust array of psychosocial treatments Manseau MW. From Patient Care to Public Health, 2018.

Specialtymims.com 54

Treating Mental Health and Opioid use Disorders

• Important considerations: benzodiazepines are not safe when

prescribed along with opioids

“opioid addiction medications buprenorphine and methadone should not be withheld from patient taking benzodiazepines or other drugs that depress the central nervous system (CNS).

combined use increases the risk of serious side effects; however, the harm caused by untreated opioid addiction can outweigh these risks.

• Careful medication management by health care professionals can reduce these risks” (US FDA 2017).

Manseau MW. From Patient Care to Public Health, 2018.

Mountainside.com 55

Treating Mental Health and Opioid use Disorders

• In addition, clinicians should be aware of potential drug interactions between MAT and psychiatric medications.

Methadone and psychiatric medications cause QT interval prolongation

Methadone confers the highest risk of overdose of the MAT options.

Methadone should not be withheld if it is deemed the best option

Monitor carefully when using other sedating medications along with methadone, or when treating a patient who uses other substances that elevate the risk of overdose, such as alcohol.


EMS12lead.com56


• Naltrexone is the most effective MAT option for individuals with AUD

• Naltrexone labelling includes warnings about mood changes for which individuals with comorbid psychiatric disorder and OUD may already be at increased risk.

• This should not be a reason to withhold this MAT option if it is the most appropriate for the patient


Stuffyoushouldknow.com 57


Mental Illness

Alc

oh

ol

an

d

Su

bst

an

ce U

se

Manseau MW. From Patient Care to Public

Health, 2018. 58


• Integrated treatment including MAT is the best approach for CODs involving OUD.

• Integrated treatment can be delivered in a variety of settings: primary care mental health specialty settings

addictions specialty settings.

• Methadone must be dispensed in official opioid treatment programs (OTPs).

• Individuals with SMI and severe addiction would most successfully be treated in an OTP or a mental health program that offers integrated dual diagnosis treatment and MAT.

Manseau MW. From Patient Care to

Public Health, 2018. 59

Summary

• Discussed medication assisted therapy

• Discussed the role of treating mental health disorders while treating opioid use disorder

• Discussed medications used to treat opioid use disorder

• Described behavioral therapies to treat opioid use disorder

• Described best practices in the use of medication assisted therapy

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Conclusion

• Medication assisted therapy (MAT) provides medications to help an individual stop opioids, therapy and counseling to prevent relapse

• Mental illness, pain, and addiction are related and all must be treated together to prevent relapse

• Medications used to prevent relapse are: methadone, buprenorphine and naltrexone

• Counselling includes cognitive behavioral therapy, dialectical behavioral therapy, and mindfulness

• Narcotics anonymous and use of motivational interviewing are also beneficial

• Relapse to using the same dose of opioid that was used before MAT can be fatal

61

References• Adler MW.NIDA Principles of Drug Addiction Treatment. 3rd ed. 2012

http://www.drugabuse.gov/sites/defacult/files/tib_mat_opioid.pdf. (Accessed May 23, 2019)

• Anderson L. Opioid use disorder. These treatments are available now. (2018) Drugs.com. https://www.drugs.com/opioid-use-disorder-1294 (Accessed 4/26/19)

• Behavioral Health Treatment and Services. SAMHSA. https://www.samhsa.gov/find-help/treatment(Accessed 4/26/19)

• Buprenorphine (package insert). Roxane Pharma, Columbus Ohio,2015.

• Day E, et al. Outpatient versus inpatient opioid detoxification: a randomized controlled trial. Journal of Substance Abuse Treatment 2010; 1:56-66.

• Davis MA, et al. Prescription opioid use among adults with mental health disorders in the United States. J AM Board Fam Med 2017; 30:407-17.

• Hooten WM. Chronic pain and mental health disorder: shared neural mechanisms, epidemiology, and treatment. 2016; Mayo Clin Proc 91(7): 955-70.

• Manseau MW. Opioid Use Disorders and Psychiatric Comorbidity. From Patient Care to Public Health, American Psychiatric Association, 2018.

• Medication-Assisted Treatment (MAT). https://fda.gov/drugs/drugsafety/informationbydrugclass/ucm600092.htm (Accessed 4/25/2019)

62

http://www.drugabuse.gov/sites/defacult/files/tib_mat_opioid.pdf

https://www.drugs.com/opioid-use-disorder-1294

https://www.samhsa.gov/find-help/treatment

https://fda.gov/drugs/drugsafety/informationbydrugclass/ucm600092.htm

References• Kapur BM et al. Methadone: a review of drug-drug and pathophysiological interactions. Crit Rev

Clin Lab Sci. 2011; 48(4):171-95.

• Logan BA et al. Neonatal abstinence syndrome: treatment and pediatric outcomes. Clin ObstetGynecol 2013; 56(1)): 186-92.

• Minozzi S et al. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev. Chichester, UK 2011; (2): CD0013333. DOI: 10.1002/14651858.CD001333.pub3. PubMed PMID: 21318150.

• NIDA Drug Facts: treatment approaches for drug addiction. 2009 http://www.drugabuse.gov/publications/drugfacts/treatment-approaches-drug-addiction. (Accessed May 22, 2019)

• NIDA Topics in brief, medication-assisted treatment for opioid addiction. 2012; http://http://wwwdrugabuse.gov/sites/defaultsites/tib_mat_opioid.pdf. (Accessed May 22, 2019)

• NIDA. Understanding Drug Abuse and Addiction. 2016. https:www.drugabuse.gov/publications/teaching-packets/understanding-drug-abuse-addiction/section-iii. (Accessed May 23, 2019)

• Office of National Drug Control Policy, Medication-Assisted Treatment for Opioid Addiction 2012. http://www.whitehourse.gov/sites/default/files/ondcp/recovery/medication_assisted _treatment_9-21-2012.pdf. (Accessed May 23, 2019)

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http://www.drugabuse.gov/publications/drugfacts/treatment-approaches-drug-addiction

http://http/wwwdrugabuse.gov/sites/defaultsites/tib_mat_opioid.pdf

http://www.whitehourse.gov/sites/default/files/ondcp/recovery/medication_assisted%20_treatment_9-21-2012.pdf

References• Probuphine(package insert). Braeburn Pharmaceutics Inc. Princeton, NJ

• Ross S. Chronic pain, mental health and substance use disorders: how can we manage this triad in our healthcare system and in our communities: 2015; Col Med Rev 1(1);57-62.

• Sublocade (package insert) North Chesterfield Virginia: Indivior PLE; 2018.

• Suboxone (package insert). North Chesterfield, Virginia: Indivior PLE; 2018

• Substance Abuse and Mental Health Services Administration, Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs: A treatment Improvement Protocol. 2008. http://store.samhsa.gov/shin/content/SMA12-4108. (Accessed May 22, 2019)

• Temple KM. Medication-assisted treatment for opioid use disorder in rural America. 2018; The Rural Monitor. https://ruralhealthinfo.org/rural-moniro/medication-assisted-treatment/ (Accessed 4/25/2019)

• Treatment of patients with substance use disorders, second edition. American Journal of Psychiatry. 2006; 163 (8 suppl):5-82.

• Vivitrol (package insert). Waltham, MA: Alkermes, Inc 2015.

• White WL, et al. Recovery-oriented methadone maintenance. The American Society of Addiction Medicine: The ASAM Criteria. 2010: 2010recovery_orientedMethadoneMaintenance.pdf (Accessed 5/22/19)

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http://store.samhsa.gov/shin/content/SMA12-4108

https://ruralhealthinfo.org/rural-moniro/medication-assisted-treatment/

Questions

65

Pharmacotherapy for Maintenance Treatment of Opioid Use Disorder

Methadone/Dosing Side Effects Monitoring Comments

Day 1:

First dose maximum:

30 mg

*5-10 mg with no or

low opioid tolerance

Day 1 Maximum:

40 mg

Typical Target:

60 mg/day or higher

associated with greater

retention

80-120 mg/day

(some patients require

higher doses)

Common: constipation,

lightheadedness,

dizziness, sedation,

nausea, vomiting,

sweating

Rare: EKG

abnormalities, psychosis,

pruitis, sexual

dysfunction, decreased

libido, amenorrhea,

weight gain, edema,

seizures, hypotension

LFTs, EKG (QTc),

pregnancy test,

serum

concentrations

(interpretation

varies-should

consider duration of

therapy and delayed

reflection of dose

adjustments in

serum; peak 2-4

hours post dosing)

•Formulation for OUD: liquid, powder

or tablets to be dissolved in water

•Daily doses for OUD are higher than

those for pain

•Titrate slowly-dose stabilization

takes weeks

•Take home methadone cannot be

considered until day 90 of treatment

•Many interactions with inhibitors

and inducers of CYP3A4 and 2C9

•Evaluate for risk factors for QTC

prolongation and do not start if QTc is

>500msec at baseline

•Consider risk/benefit of using other

opioids or CNS depressants 66


Buprenorphine/Dose Side Effects Monitoring Comments

Buccal or sublingual (SL)

buprenorphine (including

buprenorphine/ naloxone)

Initiation: 2-8 mg total on

induction day

Target: 8-16 mg/day

Maximum: 24 mg/day

*Doses up to 32 mg/day have

been studied but have not

demonstrated clinical

advantage

Common: sedation,

constipation, nausea,

headache,

hyperhidrosis, oral

hypoesthesia,

glossodynia, oral

mucosal erythema

Rare: hepatitis,

respiratory depression,

serotonin syndrome

LFTs •REMs program to educate on and

mitigate risks or accidental overdose,

misuse and abuse

•Newer formulations with greater

bioavailability of buprenorphine have

been developed, achieving the safe

effects as original formulations with

lower doses (i.e. Bunavail 4.2/0.7 mg and

Zubsolv 5.7 mg/1.4 mg are equivalent to

8 mg/2 mg Suboxone

•Doses greater >16mg/day confer 80-

95% mu-opioid receptor occupancy

67


Buprenorphine/Dosing Side Effects Monitoring Comments

Subcutaneous (SC)

buprenorphine

300 mg SC monthly x 2

months, then 100 mg SC

monthly; may increase to

300 mg SC monthly

Common: constipation,

headache, nausea,

injection site pruitis,

vomiting, increased

hepatic enzymes, fatigue,

and injection site pain

Rare: hepatitis,

respiratory depression,

serotonin syndrome

LFTs

Signs of patient attempted

removal

•REMS program because

of risk of serious

complications if

administered incorrectly

•Must NOT be dispensed

directly to patient because

of risk of embolus, if

administered

intravenously

•Must be stabilized on SL

buprenorphine >7 days

prior to initiation

68


Buprenorphine/Dosing Side Effects Monitoring Comments

Subdermal buprenorphine

implant

4 implants inserted

subdermally into upper

arm for 6 months (must be

removed by the end of the

6th month). After initial 6

months, 4 implants may be

inserted into upper arm on

opposite side for 6 months

Common:

Implant site

pain, pruitis,

erythema,

headache,

constipation,

nausea, vomiting

Rare:

Complications

from improper

insertion or

removal (nerve

damage,

migration,

embolism, and

death),

spontaneous

expulsion,

protrusion, local

migration

LFTs

Signs of

patient

attempted

removal

Examine

insertion site

one week

after

insertion

•Dosing is equivalent to 8-24 mg SL

buprenorphine

•Emergency surgical incision within 14 days of

administration is possible

•REMS program because of risk of serious

complications with insertion and removal

•Maximum duration of use is 12 months if

buprenorphine treatment still indicated, must

convert back to SL formulation

•Must be stable on SL doses <8mg/day for

>3months prior to initiation

•Each implant contains 74.2 mg buprenorphine

(equivalent to 80 mg buprenorphine SL)

•Monthly follow-up recommended for counseling

and psychosocial treatment

•Limited utility given maximum duration of 12

months, low equivalent SL daily dose, and

invasive procedure

69


Naltrexone/Dosing Side Effects Monitoring Comments

50 mg daily oral

380 mg monthly

injection

Common: nausea,

vomiting, headache,

low energy, anxiety,

depression, rash,

decreased alertness,

injection site

reactions

Rare: hepatotoxicity

LFTs •Hepatotoxicity is idiosyncratic and dose-

dependent

•Avoid in patients with acute hepatitis or liver

failure

•Must be abstinent from most opioids for 7-10

days and longer for methadone

•Opioids will not be as effective for emergency

management of pain

•Patients should carry a wallet card or medical

alert bracelet noting use in case of emergency

requiring analgesia

70

Documents

Medication Assisted Therapy - Auburn Universitypharmacy.auburn.edu/oti/pdf/oti-jackson2.pdf · Learning Objectives •Define medication assisted therapy (MAT) •Discuss medications